Chitin (N-acetyl glucosamine) is a naturally occurring polysaccharide and many of its derivatives have applications in the biomedical field. Chitosan is a deacetylated chitin derivative and the term includes a variety of polymers with different degrees of deacetlyation and depolymerization. Most chitosans are soluble at pHs below 7 and many form hydrogels when dissolved in aqueous solutions. Chitosan has been used for a variety of applications as a biomaterial for tissue engineering, wound healing, and as an excipient for drug delivery. Chitosan can be used as a drug delivery agent for a wide variety of therapeutics. For example, DNA complexation with chitosan yields suitable nano- and micro-particulate formulations for transfection in vivo and in vitro. However, both chitin and chitosan are limited in their uses due to a lack of biocompatibility.
N,O-carboxymethylchitosan (NOCC) has been generally found to be more biocompatible than the highly deacetylated and high molecular weight chitosans. The difference has been attributed to the presence of carboxymethyl groups (—CH2—COO−) along the polysaccharide chain. Unfortunately, NOCC precipitates in acidic solutions. The insolubility of NOCC is undesirable for therapeutic applications in acidic environments. There is a need for polymers with good biocompatibility and solubility in acidic, basic, and neutral environments.
Accordingly, it is an object of the invention to provide novel N-acylated chitinous polymers.
It is a further object of the invention to provide polymers with expanded solubility ranges, especially at low pH's.
It is also an object of the invention to provide polymers which have moieties capable of forming covalent or ionic bonds with agents.
It is also an object of the invention to provide a method for administering an agent to a subject using an N-acylated-N,O-carboxyalkylchitosan. The agent is linked either covalently, ionically, electrostatically, or dispersed in a mixture of the polymer, which allows the agent to be released in the subject.
It is another object of the invention to provide a method for treating a subject suffering from a disorder by administering an effective amount of an N-acylated-N,O-carboxyalkylchitosan associated with a therapeutic agent.
It is further an object of the invention to provide novel cross linked N-acylated-N,O-carboxyalkylchitosan.
These and other objects, features, and advantages of the invention will be apparent from the following description and claims.